Adhesives and Sealants
Surgical adhesives have been increasingly used to enhance or at least partially replace traditional wound closure technologies such as sutures and staples, offering improved sealing capabilities and plugging of undesired leaks.
Despite recent developments and increased clinical demand, most of the currently available products suffer from serious drawbacks. One of the drawbacks is the short time-window available for their proper application onto the treated site and another is the short time they remain adhesive after application.
United States Application Publication No. US2005069589 to Lowinger et al. describes a tissue adhesive sealant that includes a cross-linkable protein in a solution, that when combined with a cross-linking agent solution including an aldehyde and amino acid containing species reactive with the aldehyde, cross-links to form a seal.
The sealant is stated to be highly suitable for bonding tissue alone or in combination with a patch. Such a system may not be easy to use as it may limit the time-window for application of the adhesive.
International Application Publication No. WO2010146582 is directed to reinforced multi component adhesives that include an uncured and curable spreadable composition of matter, and a biocompatible inert reinforcing agent including at least one curing agent, wherein the uncured composition applied to a surface is characterized as capable of curing after adding the reinforcing agent to the uncured composition, and wherein the cured composition together with the added reinforcing agent is configured to have improved mechanical support and strength. Following placement of the fibrous component containing the curing-agent, curing process begins spontaneously. The method and system of WO2010146582 provides the ability to control the time of application of the adhesive since the second step of applying the reinforcing agent is fully controlled by the caregiver, and curing occurs only once this second step is practiced.
However, a drawback of this method may be that curing often occurs immediately upon application of the reinforcing agent. As an example, if the curable composition contains albumin and the reinforcing agent contains gluteraldehyde, the crosslinking reaction will be initiated immediately after creating contact between albumin and gluteraldehyde. As a result, the caregiver cannot improve or alter the positioning of the reinforcing agent on the surface once applied.
United States Application Publication No. US2010303891 describes a biocompatible layer that specifically delays the release of NO as an agent.
U.S. Pat. No. 6,124,373 describes a method for controlling the gelling point of a bone cement containing poly(polypropylene fumarate), a cross-linking monomer, an initiator, an inorganic filler, and a radical initiator. The gelling point is controlled by varying the molecular weight of the poly(polypropylene fumarate) while maintaining the weight average molecular weight (Mw) of the poly(polypropylene fumarate) above 2000 and the polydispersity index of the poly(polypropylene fumarate) below 2.
United States Application Publication No. US2003175327 describes haemostatic compositions useful to promote hemostasis at active bleeding wound sites. The haemostatic compositions typically include an article containing cellulose, e.g., cotton gauze, and a polysaccharide covalently linked to the cellulose, or a polysaccharide ionically cross-linked and in association with the article. Obviously, the compositions have to be capable of immediate action upon application at the bleeding site, rather than controlled action after application, and thus the compositions are prepared ex-situ and ready for use in final form well before needed. Some of the compositions include cross-linked dextran beads that incorporate cations such as Ca2+. The incorporated cations serve to promote haemostasis. The polysaccharides also serve to establish haemostasis, by size-excluding coagulation components. Additional materials may be added to make the composition adhesive.
Canadian Patent No. CA2670429 describes a gelling sealant for a medical device, the gelling sealant including: a viscoelastic material exhibiting a first viscosity during introduction into a body cavity; and a second viscosity after dwelling within the body cavity for a predetermined amount of time, the body cavity is adjacent to a medical device adapted to occlude at least a portion of the body cavity; wherein the viscoelastic material provides enhanced impermeability to the portion of the body cavity occluded by the medical device. The gelling sealant may thicken and then adhere to the inner surfaces of the body cavity after dwelling within the body cavity for a predetermined amount of time. Thickening results from crosslinks is described as being initiated by: mixing two components that are physically separated until combined in situ, or a prevalent condition in the physiological environment, such as temperature, pH, ionic strength, etc., and the cross-linking reaction rate and final viscosity are described as being dependent upon the concentration of cations in the solution.
Similarly, United States Application Publication No. US2002022676, describes in situ crosslinkable biodegradable polymer compositions which include poly(propylene fumarate) (PPF), poly(ethylene glycol)-dimethacrylate (PEG-DMA), and optionally, beta-tricalcium phosphate)beta-TCP), and a method for controlling the crosslinking characteristics of the compositions, including the optimal crosslinking temperature and the gel point, as well as the properties of the cross linked compositions such as the compressive strength and modulus and the water holding capacity. The gelling point and temperature are controlled by the amount of PEG in the composites.
Adhesion Barriers
Postoperative stiffness is one of the most common complications of shoulder surgery and is associated with pain, formation of adhesions, and limitation in motion. The pathophysiology of the stiffness complication is likely to be attributable to formation of adhesions primarily developing between the deltoid muscle and the underlying rotator cuff, in the extra-articular space. These occur frequently in cases of open anterior surgical approach to the shoulder (i.e., open reduction and internal fixation of shoulder fractures, Latarjet procedures, hemi- or total shoulder arthroplasties), and to a less extent in arthroscopic rotator cuff repairs or arthroscopic shoulder stabilizations (i.e., Bankart procedures). If the adhesion area is very small, physical therapy may be effective in “breaking” of adhesions. It is not effective, however, in the treatment of large area adhesions. Adhesions may also occur in shoulder fractures not treated surgically or secondary to blunt shoulder trauma. Other joints such as the elbow and knee can be similarly affected. Up-to-date, none of commercial adhesion prevention products, currently used in pelvic and abdominal surgeries, are available for adhesion prevention after rotator cuff repair surgeries, open reduction and internal fixation of shoulder fractures, Latarjet procedures, hemi- or total shoulders, arthroscopic Bankart procedures, blunt shoulder trauma, non surgically treated, shoulder fractures, elbow trauma or trauma or surgery about the knee.
A possible solution to prevent the formation of post-operative adhesions is the use of a mechanical barrier to prevent contact between the damaged muscle layers, and enable tissue healing with minimal scar formation. Currently, there is a range of adhesion prevention products, such as Interceed (J&J), Seprafilm etc., used in pelvic and abdominal surgical procedures (Ahmad G, et al. Cochrane Database Syst Rev. 2008 Apr. 16; (2)).
The use of alginate as a promising biomaterial in terms of adhesion prevention has been recently proposed (Chaturvedi A A, et al. Br J Surg. 2013 June; 100(7):904-10; Chaturvedi A. A., et al. J Surg Res. 2014 Jun. 4. pii: S0022-4804(14)00548-4). In animal models, alginate gels have been reported to attenuate postoperative intraperitoneal adhesions following caecal abrasion (Chaturvedi 2013, ibid.) and repair of colon anastomoses (Chaturvedi 2014, ibid.). However, none of the aforementioned materials have been designed and used for adhesion prevention after rotator cuff repair surgeries, open shoulder surgery, blunt shoulder trauma, shoulder fractures, elbow trauma or trauma or surgeries about the knee.
U.S. Pat. No. 5,266,326 describes a method of modifying salts of alginic acid in situ, to form an insoluble gel, for prevention and treatment of various intra-articular and extra-articular (spine) complications.
U.S. Pat. No. 6,693,089 describes a method of reducing adhesion at a site of trauma, which includes forming a film from an alginate solution, contacting the film with a cross-linking solution to form a cross-linked mechanically stable sheet, and placing at least a portion of the sheet at the site of trauma. U.S. Pat. No. 6,693,089 further relates to an anti-adhesion barrier including a sheet of ionically cross-linked alginate having a thickness in a range of 0.25 mm to 10 mm.
International Application Publication No. WO 2010/117266 relates to a dispensing system that can be used to introduce a gel-forming fluid into or onto the body that will produce a homogeneous gel in situ.